We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Longitudinally Extensive Transverse Myelitis With and Without Aquaporin 4 Antibodies

Joanna Kitley, BMBS1; Maria Isabel Leite, DPhil1; Wilhelm Küker, FRCR2; Gerardine Quaghebeur, FRCR2; Jithin George, BMBS1; Patrick Waters, PhD1; Mark Woodhall, PhD1; Angela Vincent, FRS1; Jacqueline Palace, DM1
[+] Author Affiliations
1Nuffield Department of Clinical Neurosciences, Oxford University Hospitals NHS Trust, University of Oxford, Oxford, England
2Department of Neuroradiology, Oxford University Hospitals NHS Trust, Oxford, England
JAMA Neurol. 2013;70(11):1375-1381. doi:10.1001/jamaneurol.2013.3890.
Text Size: A A A
Published online

Importance  Aquaporin 4 antibody (AQP4-Ab)–negative patients with longitudinally extensive transverse myelitis (LETM) behave differently from those with AQP4-Ab. Aquaporin 4 antibody–negative neuromyelitis optica (NMO) is rare when good assays are used.

Objective  To assess if AQP4-Ab–negative patients with LETM share similar disease characteristics with AQP4-Ab–positive patients or whether they have distinct features and alternative diagnoses.

Design  We collated clinical and paraclinical data on patients with LETM identified through the Oxford NMO clinical database. Aquaporin 4 antibodies were tested using 2 sensitive assays. We describe the features of patients with LETM, compare findings between patients with and without AQP4-Ab, and describe alternative diagnoses in AQP4-Ab–negative patients.

Setting  Single specialist UK center for NMO.

Participants  Seventy-six adult patients with LETM.

Main Outcomes and Measures  Comparison of clinical and paraclinical data.

Results  Fifty-eight percent of patients were AQP4-Ab positive. Alternative diagnoses could usually be identified in AQP4-Ab–negative patients, including those fulfilling NMO diagnostic criteria. Only 6.5% of patients had “true” seronegative NMO and 6.5% had idiopathic LETM. There were some important differences between AQP4-Ab–positive and –negative cases, including older onset age, higher proportion of females, lower incidence of simultaneous optic neuritis, lower frequency of conus involvement, and higher prevalence of coexisting autoimmune disorders in AQP4-Ab–positive cases. Attack severity and degree of recovery were similar in the 2 groups.

Conclusions and Relevance  Patients with LETM without AQP4-Ab include a number of different diagnostic categories and it is not surprising therefore that they show important differences compared with AQP4-Ab–positive patients, even when considering only those fulfilling current NMO diagnostic criteria. Thus, we suggest that diagnoses such as myelin-oligodendrocyte glycoprotein antibody disease, multiple sclerosis, acute disseminated encephalomyelitis, and postinfectious disorders should be exclusions in the NMO diagnostic criteria and AQP4-Ab–positive and antibody–negative NMO/NMO spectrum disorder cohorts should be analyzed separately.

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal


Place holder to copy figure label and caption
Figure 1.
Kaplan-Meier Analysis Showing Cumulative Probability of Relapse of Central Nervous System Inflammation Over Time Following Longitudinally Extensive Transverse Myelitis (LETM)

There was a trend toward greater probability of relapsing over time in patients positive for aquaporin 4 antibodies (AQP4-Ab) compared with patients without AQP4-Ab (P = .07), although the likelihood of early relapse (in the first 18 months) appeared similar.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Diagnoses of Patients With Longitudinally Extensive Transverse Myelitis (LETM)

Fifty-eight percent of patients with LETM were positive for aquaporin 4 antibodies (AQP4-Ab). Alternative diagnoses could be identified in the majority of the remaining patients; these included myelin-oligodendrocyte glycoprotein antibody (MOG-Ab) disease, infection, and other inflammatory disorders. Because all patients were referred to a specialist center for neuromyelitis optica (NMO), the proportion of patients with inflammatory causes may be overrepresented in our center. ADEM indicates acute disseminated encephalomyelitis and MS, multiple sclerosis.

Graphic Jump Location




Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 5

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles